Xiang Jingjing, Cai Liangliang, Wang Qin, Zhu Yonghong, Han Yong
Department of Pharmacy, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, China.
Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, China.
Front Chem. 2025 Jan 13;12:1534132. doi: 10.3389/fchem.2024.1534132. eCollection 2024.
Selpercatinib, a selective RET kinase inhibitor, is approved for treating various cancers with RET gene mutations such as RET-rearranged thyroid cancer and non-small cell lung cancer. The presence of process-related and degradation impurities in its active pharmaceutical ingredient (API) can significantly affect its safety and effectiveness. However, research on detecting these impurities is limited.
This study developed and systematically validated a High-Performance Liquid Chromatography (HPLC) method for identifying selpercatinib and its related impurities. The method utilized a 4.6 mm × 250 mm chromatographic column with 5 μm particles, employing a flow rate of 1.0 mL/min, a detection wavelength of 235 nm, an injection volume of 10 μL, and a column temperature of 35°C. Mobile phase A was composed of a 9:1 ratio of water to acetonitrile, with the aqueous component adjusted to pH 2.5 and containing 2 mM potassium dihydrogen phosphate (KHPO) and 0.4% triethylamine. Mobile phase B was pure acetonitrile. The gradient elution program was as follows: 0-2 min, 5%B; 2-15 min, 5% to 15%B; 15-30 min, 15% to 35%B; 30-35 min, 35% to 45%B; 35-36 min, 45% to 5%B; 36-45 min, 5%B.
The chromatographic method established in this study was validated according to the ICH Q2 (R1) guidelines. The developed HPLC method demonstrated excellent specificity, sensitivity, stability, linearity, precision, accuracy, and robustness. It efficiently separated the impurities present in selpercatinib, thereby confirming the method's efficacy in ensuring the purity and quality of the drug.
The chromatographic method established in this study can be used for the detection of selpercatinib and its impurities, providing significant reference value for the quality research of selpercatinib bulk drug and its preparations, and ensuring the safety of medication for patients.
塞尔帕替尼是一种选择性RET激酶抑制剂，被批准用于治疗各种具有RET基因突变的癌症，如RET重排的甲状腺癌和非小细胞肺癌。其活性药物成分（API）中工艺相关杂质和降解杂质的存在会显著影响其安全性和有效性。然而，关于检测这些杂质的研究有限。
本研究开发并系统验证了一种用于鉴定塞尔帕替尼及其相关杂质的高效液相色谱（HPLC）方法。该方法使用一根4.6毫米×250毫米、填料粒径为5微米的色谱柱，流速为1.0毫升/分钟，检测波长为235纳米，进样量为10微升，柱温为35°C。流动相A由水与乙腈按9:1的比例组成，水相调节至pH 2.5，并含有2毫摩尔磷酸二氢钾（KHPO）和0.4%三乙胺。流动相B为纯乙腈。梯度洗脱程序如下：0 - 2分钟，5%B；2 - 15分钟，5%至15%B；15 - 30分钟，15%至35%B；30 - 35分钟，35%至45%B；35 - 36分钟，45%至5%B；36 - 45分钟，5%B。
本研究建立的色谱方法按照ICH Q2（R1）指南进行了验证。所开发的HPLC方法具有出色的特异性、灵敏度、稳定性、线性、精密度、准确度和耐用性。它有效地分离了塞尔帕替尼中存在的杂质，从而证实了该方法在确保药物纯度和质量方面的有效性。
本研究建立的色谱方法可用于检测塞尔帕替尼及其杂质，为塞尔帕替尼原料药及其制剂的质量研究提供了重要参考价值，并确保患者用药安全。
